Health care workers' self-perceived meaning of residential care work.

BACKGROUND: Attracting and supporting a sustainable long-term care (LTC) workforce has been a persistent social policy challenge across the globe. To better attract and retain a sustainable LTC workforce, it is necessary to adopt a unified concept of worker well-being. Meaning of work is an important psychological resource that buffers the negative impacts of adverse working conditions on workers' motivation, satisfaction, and turnover intention. The aim of this study was to explore the positive meaning of care work with older people and its implications for health care workers' job satisfaction and motivation to work in the LTC sector. METHODS: This study adopted a qualitative descriptive design that pays particular attention to health care workers; such as nurses, personal care workers; as active agents of the meaning making and reframing of care work in LTC communities in a East Asia city. In-depth semi-structured interviews were conducted with thirty health care workers in LTC communities in Hong Kong. Thematic analysis was employed for data analysis. RESULTS: The research findings indicate that while health care workers perform demanding care work and experience external constraints, they actively construct positive meanings of care work with older people as a helping career that enables them to facilitate the comfortable aging of older people, build affectional relationships, achieve professional identity, and gain job security. CONCLUSIONS: This qualitative study explores how health care workers negotiate the positive meaning of older people care work and the implications of meaningful work for workers' job satisfaction and motivation to work in the LTC sector. The importance of a culturally sensitive perspective in researching and developing social policy intervention are suggested.

[Effect of Staphylococcal Nuclease and Tudor Domain Containing 1/SLC7A11 on the Occurrence and Development of Osteosarcoma by Inhibiting Ferroptosis].

Objective To investigate the effect of staphylococcal nuclease and tudor domain containing 1(SND1) on the biological function of osteosarcoma cells and decipher the mechanism of SND1 in regulating ferroptosis in osteosarcoma cells via SLC7A11. Methods Human osteoblasts hFOB1.19 and osteosarcoma cell lines Saos-2,U2OS,HOS,and 143B were cultured,in which the expression level of SND1 was determined.Small interfering RNA was employed to knock down the expression of SND1(si-SND1) in the osteosarcoma cell line HOS and 143B.The CCK8 assay kit,colony formation assay,and Transwell assay were employed to examine the effect of SND1 expression on the biological function of osteosarcoma cells.Furthermore,we altered the expression of SND1 and SLC7A11 in osteosarcoma cells to investigate the effect of SND1 on osteosarcoma ferroptosis via SLC7A11. Results The mRNA and protein levels of SND1 in Saos-2,U2OS,HOS,and 143B cells were higher than those in hFOB1.19 cells(all P<0.01).Compared with the control group,transfection with si-SND1 down-regulated the expression level of SND1 in HOS and 143B cells(all P<0.01),decreased the viability of HOS and 143B cells,reduced the number of colony formation,and inhibited cell invasion and migration(all P<0.001).The ferroptosis inducer Erastin promoted the apoptosis of HOS and 143B cells,while the ferroptosis inhibitor Ferrostatin-1 improved the viability of HOS and 143B cells(all P<0.001).After SND-1 knockdown,Erastin reduced the viability of HOS and 143B cells,while Ferrostatin-1 restored the cell viability(all P<0.001).After treatment with Erastin in the si-SND1 group,the levels of iron and malondialdehyde were elevated,and the level of glutathione was lowered(all P<0.001).The results of in vivo experiments showed that SND1 knockdown inhibited the mass of the transplanted tumor in 143B tumor-bearing nude mice(P<0.001).Knocking down the expression of SND1 resulted in down-regulated SLC7A11 expression(all P<0.001) and increased ferroptosis in HOS and 143B cells(P<0.001,P=0.020). Conclusions SND1 presents up-regulated expression in osteosarcoma cells.It may inhibit ferroptosis by up-regulating the expression of SLC7A11,thereby improving the viability of osteosarcoma cells.

Decreased basal ganglia and thalamic iron in early psychotic spectrum disorders are associated with increased psychotic and schizotypal symptoms.

Iron deficits have been reported as a risk factor for psychotic spectrum disorders (PSD). However, examinations of brain iron in PSD remain limited. The current study employed quantitative MRI to examine iron content in several iron-rich subcortical structures in 49 young adult individuals with PSD (15 schizophrenia, 17 schizoaffective disorder, and 17 bipolar disorder with psychotic features) compared with 35 age-matched healthy controls (HC). A parametric approach based on a two-pool magnetization transfer model was applied to estimate longitudinal relaxation rate (R1), which reflects both iron and myelin, and macromolecular proton fraction (MPF), which is specific to myelin. To describe iron content, a synthetic effective transverse relaxation rate (R2*) was modeled using a linear fitting of R1 and MPF. PSD patients compared to HC showed significantly reduced R1 and synthetic R2* across examined regions including the pallidum, ventral diencephalon, thalamus, and putamen areas. This finding was primarily driven by decreases in the subgroup with schizophrenia, followed by schizoaffective disorder. No significant group differences were noted for MPF between PSD and HC while for regional volume, significant reductions in patients were only observed in bilateral caudate, suggesting that R1 and synthetic R2* reductions in schizophrenia and schizoaffective patients likely reflect iron deficits that either occur independently or precede structural and myelin changes. Subcortical R1 and synthetic R2* were also found to be inversely related to positive symptoms within the PSD group and to schizotypal traits across the whole sample. These findings that decreased iron in subcortical regions are associated with PSD risk and symptomatology suggest that brain iron deficiencies may play a role in PSD pathology and warrant further study.

Synthesis and characterization of a novel 68Ga-labeled p-bromobenzyl lysine-urea-ODAP PSMA inhibitor.

Prostate-specific membrane antigen (PSMA) has been proved as a specific target for diagnosis and treatment of prostate cancer (PCa). Recently, oxalyldiaminopropionic acid (ODAP)-Urea-based ligands showed the potential as a new scaffold for developing radiotracers to image PCa. In this study, we synthesized seven ODAP-Urea-Lys derivatives characterized with p-bromobenzyl group conjugated to lysine. The ligands showed medium-to-high potency, with Ki values ranging from 27.9 nM to 0.94 nM. The ligands could be efficiently radiolabeled with 68Ga, in high purity. Radioligands were stable and showed PSMA specific cellular uptake, in PSMA++ LNCaP cells and PSMA+ 22Rv1 cells over PSMA- PC3 cells. MicroPET imaging was performed in 22Rv1 tumor-bearing mice and 68Ga-ligand-1 showed the best characteristics among the seven ligands, with the highest tumor uptake (SUVmax: 0.56 ± 0.07). A biodistribution study was also performed. ODAP-Urea-Lys-p-bromobenzyl could be used to image prostate cancer in vivo, and the ligands could have high binding potency. The future investigation is still necessary to improve the tumor-specific uptake of this class of ligands and reducing the non-specific uptake in normal organs.

Asymmetric Janus functionalization induced magnetization and switchable out-of-plane polarization in 2D MXene Mo2CXX'.

Exploring two-dimensional (2D) van der Waals materials with out-of-plane polarization and electromagnetic coupling is essential for the development of next-generation nano-memory devices. A novel class of 2D monolayer materials with predicted spin-polarized semi-conductivity, partially compensated antiferromagnetic (AFM) order, fairly high Curie temperature, and out-of-plane polarization is analyzed in this work for the first time. Based on density functional theory calculations, we systematically studied these properties in asymmetrically functionalized MXenes (Janus Mo2C)-Mo2CXX' (X, X' = F, O, and OH). Using ab initio molecular dynamics (AIMD) and phonon spectrum calculations, the thermal and dynamic stabilities of six functionalized Mo2CXX' were identified. Our DFT+U calculation results also provided a switching path for out-of-plane polarizations, where the reverse of electric polarization is driven by terminal-layer atom flipping. More importantly, strong coupling between magnetization and electric polarization originating from spin-charge interactions was observed in this system. Our results confirm that Mo2C-FO would be a novel monolayer electromagnetic material, and its magnetization can be modulated by electric polarization.

Alkane production from fatty alcohols by the combined reactions catalyzed by an alcohol dehydrogenase and an aldehyde-deformylating oxygenase.

PsADH, an alcohol dehydrogenase originating in Pantoea sp. was characterized and found to convert a broad variety of fatty alcohols into their corresponding aldehydes, the substrates of alkane biosynthesis. By coupling PsADH with NpAD, a cyanobacterial aldehyde-deformylating oxygenase, and by optimizing the conditions of the enzyme-catalyzed reactions, we achieved a 52% conversion of 1-tetradecanol to tridecane. We further applied this system to generate alkanes ranging from C5-17. These alkanes can be used as biofuels, suggesting that introducing a suitable alcohol dehydrogenase is an effective strategy to utilize fatty alcohols for alkane production.

Effects of posture on heart rate variability in non-frail and prefrail individuals: a cross-sectional study.

BACKGROUND: Frailty is an aging-related syndrome leading to high mortality in older adults. Without effective assessment and prevention of frailty, the incidence of frailty and relevant adverse outcomes will increase by 2050 as worldwide populations age. Although evidence suggested heart rate variability (HRV) is a potential measure of frailty, the role of HRV in frailty assessment remains unclear because of controversial findings. This study examined the effects of posture on HRV parameters in non-frail and prefrail individuals to understand the role of HRV in assessing frailty. METHODS: Forty-six participants aged ≥ 50 years were recruited between April and August 2022. Frailty was defined using Fried's criteria. HRV was measured in standing, sitting, and lying postures, respectively, using a Polar Watch, and analyzed using Kubios HRV Standard 3.5.0 (Kubios). The five most commonly used parameters were examined, including standard deviations of all normal-to-normal intervals (SDNN), root mean square of the successive differences (RMSSD), low frequency (LF), high frequency (HF), and LF/HF. Independent t-tests and Mann-Whitney tests were used for inter-group comparisons. Friedman tests were used for intra-group comparisons across postures. RESULTS: The non-frail group showed significant differences in HRV parameters across postures (all p < 0.05), whereas the prefrail group did not demonstrate any difference (all p > 0.05). The differences in the non-frail group included higher RMSSD and HF in the lying posture compared to those in the standing posture (29.54 vs 21.99 p = 0.003, 210.34 vs 96.34 p = 0.001, respectively), and higher LF and LF/HF in the sitting posture compared to those in the lying posture (248.40 vs 136.29 P = 0.024, 1.26 vs 0.77 p = 0.011, respectively). CONCLUSIONS: The effects of posture on HRV were blunted in the prefrail group, which suggests an impaired cardiac autonomic functioning. Measuring the effects of posture on HRV parameters may contribute to frailty assessment. However, further evidence from larger cohorts and including additional HRV parameters is needed.

Synthesis and Performance Evaluation of a Novel High-Temperature-Resistant Thickener.

Successful exploitation of carbonate reservoirs relies on the acid-fracturing process, while the thickeners used in this process play a key role. It is a common engineering problem that thickeners usually fail to function when used in high-temperature environments. Until now, no research has ventured into the field of synthesizing thickeners which can be effectively used at ultra-high temperatures up to 180 °C. In our current study, a novel high-temperature-resistant polyacrylamide thickener named SYGT has been developed. The thermal gravimetric analysis (TGA) reveals that SYGT is capable of withstanding temperatures of up to 300 °C. Both our scanning electron microscopy (SEM) and rheological analysis demonstrate that the SYGT exhibits excellent resistance to both temperature and shear. At 180 °C, the viscosity of the SYGT aqueous solution is no lower than 61.7 mPa·s at a 20% H+ concentration or high salt concentration, and the fracture conductivity of the thickened acid reaches 6 D·cm. For the first time, the influence of the polymer spatial network's structural parameters on the viscosity of polymer solutions has been evaluated quantitatively. It was discovered that the length and surrounding area of the SNS skeleton have a synergistic effect on the viscosity of the polymer solution. Our experiments show that SYGT effectively reduces the acid-rock reaction rate and filtration loss under harsh working conditions such as high temperature, strong shear, high salinity, and a high concentration of acid. The synthesized acid-fracturing thickener (SYGT) has wide application potential in the development of carbonate reservoirs under high-temperature conditions.

[Association of gene polymorphisms of MyD88 and TICAM1 and their interactions with community-acquired pneumonia in children]. / MyD88和TICAM1åŸºå› å¤šæ€æ€§åŠå ¶äº¤äº’ä½œç”¨ä¸Žå„¿ç«¥ç¤¾åŒºèŽ·å¾—æ€§è‚ºç‚Žçš„å ³è”ç ”ç©¶.

OBJECTIVES: To investigate the association of single nucleotide polymorphisms (SNPs) of myeloid differentiation factor 88 (MyD88) and Toll-like receptor adaptor molecule 1 (TICAM1) and their interactions with community-acquired pneumonia (CAP) in children. METHODS: Improved multiple ligase detection reaction assay was used for detecting the polymorphisms of nine tagging SNPs of the MyD88 and TICAM1 genes in 375 children with CAP who attended the Department of Pediatrics of the Second Affiliated Hospital of Yan'an University Medical School from August 2015 to September 2017 and 306 healthy children who underwent physical examination. A logistic regression analysis was used to evaluate the association between the distribution of genotypes and their interactions with CAP in children. RESULTS: The polymorphism of the TICAM1 gene at rs11466711T/C locus was closely associated with the susceptibility to CAP in children (P<0.05). The AA genotype of rs35747610G/A locus significantly reduced risk of sepsis in children with CAP (P<0.05). The AA genotype of rs6510826G/A locus was significantly associated with the increase in C-reactive protein level in children with CAP (P<0.05). The GG genotype of the MyD88 gene at rs7744A/G locus significantly increased the risk of respiratory failure and circulatory failure (P<0.05). The multiplicative interactions between MyD88 gene rs7744A/G and TICAM1 gene rs11466711T/C, rs2292151G/A, rs35299700C/T, and rs35747610G/A loci were significantly associated with the susceptibility to CAP, the severity of CAP, and the risk of sepsis in children (P<0.05). CONCLUSIONS: The gene polymorphisms of MyD88 and TICAM1 and their interactions are closely associated with CAP in children, with a synergistic effect on the development and progression of CAP in children.

Cortical myelin profile variations in healthy aging brain: A T1w/T2w ratio study.

Demyelination is observed in both healthy aging and age-related neurodegenerative disorders. While the significance of myelin within the cortex is well acknowledged, studies focused on intracortical demyelination and depth-specific structural alterations in normal aging are lacking. Using the recently available Human Connectome Project Aging dataset, we investigated intracortical myelin in a normal aging population using the T1w/T2w ratio. To capture the fine changes across cortical depths, we employed a surface-based approach by constructing cortical profiles traveling perpendicularly through the cortical ribbon and sampling T1w/T2w values. The curvatures of T1w/T2w cortical profiles may be influenced by differences in local myeloarchitecture and other tissue properties, which are known to vary across cortical regions. To quantify the shape of these profiles, we parametrized the level of curvature using a nonlinearity index (NLI) that measures the deviation of the profile from a straight line. We showed that NLI exhibited a steep decline in aging that was independent of local cortical thinning. Further examination of the profiles revealed that lower T1w/T2w near the gray-white matter boundary and superficial cortical depths were major contributors to the apparent NLI variations with age. These findings suggest that demyelination and changes in other T1w/T2w related tissue properties in normal aging may be depth-specific and highlight the potential of NLI as a unique marker of microstructural alterations within the cerebral cortex.

Utilizing Alcohol for Alkane Biosynthesis by Introducing a Fatty Alcohol Dehydrogenase.

Alkanes produced by microorganisms are expected to be an alternative to fossil fuels as an energy source. Microbial synthesis of alkanes involves the formation of fatty aldehydes via fatty acyl coenzyme A (acyl-CoA) intermediates derived from fatty acid metabolism, followed by aldehyde decarbonylation to generate alkanes. Advancements in metabolic engineering have enabled the construction of such pathways in various microorganisms, including Escherichia coli. However, endogenous aldehyde reductases in the host microorganisms are highly active in converting fatty aldehydes to fatty alcohols, limiting the substrate pool for alkane production. To reuse the alcohol by-product, a screening of fatty alcohol-assimilating microorganisms was conducted, and a bacterial strain, Pantoea sp. strain 7-4, was found to convert 1-tetradecanol to tetradecanal. From this strain, an alcohol dehydrogenase, PsADH, was purified and found to be involved in 1-tetradecanol-oxidizing reaction. Subsequent heterologous expression of the PsADH gene in E. coli was conducted, and recombinant PsADH was purified for a series of biochemical characterizations, including cofactors, optimal reaction conditions, and kinetic parameters. Furthermore, direct alkane production from alcohol was achieved in E. coli by coexpressing PsADH with a cyanobacterial aldehyde-deformylating oxygenase and a reducing system, including ferredoxin and ferredoxin reductase, from Nostoc punctiforme PCC73102. The alcohol-aldehyde-alkane synthetic route established in this study will provide a new approach to utilizing fatty alcohols for the production of alkane biofuel. IMPORTANCE Alcohol dehydrogenases are a group of enzymes found in many organisms. Unfortunately, studies on these enzymes mainly focus on their activities toward short-chain alcohols. In this study, we discovered an alcohol dehydrogenase, PsADH, from the bacterium Pantoea sp. 7-4, which can oxidize 1-tetradecanol to tetradecanal. The medium-chain aldehyde products generated by this enzyme can serve as the substrate of aldehyde-deformylating oxygenase to produce alkanes. The enzyme found in this study can be applied to the biosynthetic pathway involving the formation of medium-chain aldehydes to produce alkanes and other valuable compounds.

Tailoring physical properties of WS2 nanosheets by defects control.

The controllable growth of high-quality transition metal dichalcogenides (TMDs) is crucial for their device applications, which rely on the atomic and quantitative understanding of the growth mechanism of TMDs. In this work, we propose a comprehensive picture of the growth of WS2 nanosheets via Monte Carlo simulation, and an extension of diffusion-limited growth under transition state theory is developed to describe heteroepitaxy growth of WS2. Theoretical results are in good agreement with the results of chemical vapor deposition that growth temperature dominates growth processes leading to samples with various densities of vacancy defects. The vacancy defects modify the photoluminescence and ferromagnetic behavior. Our work provides a pathway toward realizing controllable physical properties in 2D materials.

Engineering cofactor metabolism for improved protein and glucoamylase production in Aspergillus niger.

BACKGROUND: Nicotinamide adenine dinucleotide phosphate (NADPH) is an important cofactor ensuring intracellular redox balance, anabolism and cell growth in all living systems. Our recent multi-omics analyses of glucoamylase (GlaA) biosynthesis in the filamentous fungal cell factory Aspergillus niger indicated that low availability of NADPH might be a limiting factor for GlaA overproduction. RESULTS: We thus employed the Design-Build-Test-Learn cycle for metabolic engineering to identify and prioritize effective cofactor engineering strategies for GlaA overproduction. Based on available metabolomics and 13C metabolic flux analysis data, we individually overexpressed seven predicted genes encoding NADPH generation enzymes under the control of the Tet-on gene switch in two A. niger recipient strains, one carrying a single and one carrying seven glaA gene copies, respectively, to test their individual effects on GlaA and total protein overproduction. Both strains were selected to understand if a strong pull towards glaA biosynthesis (seven gene copies) mandates a higher NADPH supply compared to the native condition (one gene copy). Detailed analysis of all 14 strains cultivated in shake flask cultures uncovered that overexpression of the gsdA gene (glucose 6-phosphate dehydrogenase), gndA gene (6-phosphogluconate dehydrogenase) and maeA gene (NADP-dependent malic enzyme) supported GlaA production on a subtle (10%) but significant level in the background strain carrying seven glaA gene copies. We thus performed maltose-limited chemostat cultures combining metabolome analysis for these three isolates to characterize metabolic-level fluctuations caused by cofactor engineering. In these cultures, overexpression of either the gndA or maeA gene increased the intracellular NADPH pool by 45% and 66%, and the yield of GlaA by 65% and 30%, respectively. In contrast, overexpression of the gsdA gene had a negative effect on both total protein and glucoamylase production. CONCLUSIONS: This data suggests for the first time that increased NADPH availability can indeed underpin protein and especially GlaA production in strains where a strong pull towards GlaA biosynthesis exists. This data also indicates that the highest impact on GlaA production can be engineered on a genetic level by increasing the flux through the pentose phosphate pathway (gndA gene) followed by engineering the flux through the reverse TCA cycle (maeA gene). We thus propose that NADPH cofactor engineering is indeed a valid strategy for metabolic engineering of A. niger to improve GlaA production, a strategy which is certainly also applicable to the rational design of other microbial cell factories.

Comparative genomics of the aconidial Aspergillus niger strain LDM3 predicts genes associated with its high protein secretion capacity.

Aspergillus niger is widely used as a cell factory for homologous and heterologous protein production. As previous studies reported that reduced sporulation favors protein secretion in A. niger, in this study, we conducted a comparative genomic analysis of the non-sporulating industrially exploited A. niger strain LDM3 in China and the reference protein secretion strain CBS 513.88 to predict the key genes that might define the genetic basis of LDM3's high protein-producing potential in silico. After sequencing using a hybrid approach combining Illumina and PacBio sequencing platforms, a high-quality genome sequence of LDM3 was obtained which harbors 11,209 open reading frames (ORFs). LDM3 exhibits large chromosomal rearrangements in comparison to CBS 513.88. An alignment of the two genome sequences revealed that the majority of the 457 ORFs uniquely present in LDM3 possessed predicted functions in redox pathways, protein transport, and protein modification processes. In addition, bioinformatic analyses revealed the presence of 656 ORFs in LDM3 with non-synonymous mutations encoding for proteins related to protein translation, protein modification, protein secretion, metabolism, and energy production. We studied the impact of two of these on protein production in the established lab strain N402. Both tupA and prpA genes were selected because available literature suggested their involvement in asexual sporulation of A. niger. Our co-expression network analysis supportively predicted the role of tupA in protein secretion and the role of prpA in energy generation, respectively. By knockout experiments, we showed that the ΔtupA mutant displayed reduced sporulation (35%) accompanied by higher total protein secretion (65%) compared to its parental strain. Such an effect was, however, not observed in the ΔprpA mutant.

Ultrahigh position sensitivity and fast optical relaxation time of lateral photovoltaic effect in Sb2Se3/p-Si junctions.

A large lateral photovoltaic (LPV) effect with good linearity and fast response time is necessary for developing high-performance position-sensitive detectors (PSD). In this paper, we investigated the influence of the resistance of Sb2Se3 film and the Si on the LPV properties of the Sb2Se3/p-Si junctions. The LPV exhibits a linear dependence on the laser spot position, with a maximum position sensitivity as high as 448 mV/mm. The optical relaxation time of the LPV was about 4.98 µs, which was due to the formation of the inversion layer at the Sb2Se3/p-Si interface. Our results revealed that the high resistivity of Sb2Se3 film facilitate the LPV and confirmed the resistivity of Si substrate play a key role in the LPV properties. The giant position sensitivity and fast relaxation times of the LPV suggest that the Sb2Se3/p-Si junction is a promising candidate for a wide range of optoelectronic device applications.

Autonomous Microsystems for Downhole Applications: Design Challenges, Current State, and Initial Test Results.

This paper describes two platforms for autonomous sensing microsystems that are intended for deployment in chemically corrosive environments at elevated temperatures and pressures. Following the deployment period, the microsystems are retrieved, recharged, and interrogated wirelessly at close proximity. The first platform is the Michigan Micro Mote for High Temperature (M³HT), a chip stack 2.9 × 1.1 × 1.5 mm³ in size. It uses RF communications to support pre-deployment and post-retrieval functions, and it uses customized electronics to achieve ultralow power consumption, permitting the use of a chip-scale battery. The second platform is the Environmental Logging Microsystem (ELM). This system, which is 6.5 × 6.3 × 4.5 mm³ in size, uses the smallest suitable off-the-shelf electronic and battery components that are compatible with assembly on a flexible printed circuit board. Data are stored in non-volatile memory, permitting retrieval even after total power loss. Pre-deployment and post-retrieval functions are supported by optical communication. Two types of encapsulation methods are used to withstand high pressure and corrosive environments: an epoxy filled volume is used for the M³HT, and a hollow stainless-steel shell with a sapphire lid is used for both the M³HT and ELM. The encapsulated systems were successfully tested at temperature and pressure reaching 150 °C and 10,000 psi, in environments of concentrated brine, oil, and cement slurry. At elevated temperatures, the limited lifetimes of available batteries constrain the active deployment period to several hours.

Near-ultraviolet lateral photovoltaic effect in Fe3O4/3C-SiC Schottky junctions.

In this paper, we report a sensitive lateral photovoltaic effect (LPE) in Fe3O4/3C-SiC Schottky junctions with a fast relaxation time at near-ultraviolet wavelengths. The rectifying behavior suggests that the large build-in electric field was formed in the Schottky junctions. This device has excellent position sensitivity as high as 67.8 mV mm-1 illuminated by a 405 nm laser. The optical relaxation time of the LPE is about 30 µs. The fast relaxation and high positional sensitivity of the LPE make the Fe3O4/3C-SiC junction a promising candidate for a wide range of ultraviolet/near-ultraviolet optoelectronic applications.

Cortistatin Inhibits NLRP3 Inflammasome Activation of Cardiac Fibroblasts During Sepsis.

BACKGROUND: Cortistatin is a recently discovered neuropeptide that has emerged as a potential endogenous antiinflammatory peptide. As a clinical syndrome, sepsis occurs when an infection becomes amplified, leading to organ dysfunction or risk for secondary infection. Human septic shock involves excessive inflammatory cytokine production. Interleukin (IL) 1ß is one of these cytokines, and it plays a pivotal role in sepsis-induced myocardial dysfunction. The aim of the present study is to evaluate whether cortistatin inhibits nucleotide-binding oligomerization domain-like receptor with a pyrin-domain 3 (NLRP3) inflammasome/caspase-1/IL-1ß pathway in cardiac fibroblasts (CFs) and whether this role can subsequently affect myocardial injury. METHODS AND RESULTS: To test these processes, a murine model of cecal ligation and puncture in vivo and lipopolysaccharide-induced cardiac fibroblasts were used in vitro. We found that pretreatment with cortistatin inhibited NLRP3-mediated ASC pyroptosome formation, caspase-1 activation, and IL-1ß secretion. Additionally cortistatin inhibits proinflammatory pathways (nuclear factor κB and pro-IL-1ß). CONCLUSIONS: This work provided the first evidence of cortistatin as a new immunomodulatory factor with the capacity to deactivate NLRP3 inflammasome activity and to protect against the myocardial injury induced by sepsis. This study has important implications for the design of new strategies to control NLRP3-related diseases.

[Roles of hMMS2 gene in reversing the oxaliplatin tolerance of human colon carcinoma cells].

In this study, the roles of hMMS2 (human methyl methanesulfonate sensitive mutant 2) gene encoding the human ubiquitin-conjugating enzyme E2 variant 2 in the drug resistance in human colon carcinoma were investigated by using a well-differentiated human colorectal carcinoma L-OHP-resistant cell line, THC8307/L-OHP. THC8307/L-OHP cells were transfected via liposome along with plasmid pcDNA6.2-GW/EmGFP-miR-MMS2 expressing both miRNA against hMMS2 and GFP, followed by real-time fluorescent quantitative PCR and immunofluorescence to select stable transfectants with significantly reduced hMMS2 expression. Compared with untransfected or pcDNA6.2-GW/EmGFP vector-transfected cells, the hMMS2-depleted cells displayed significantly (P<0.05) reduced half inhibition concentration(IC50) resistance index (RI) and colony-forming efficiency (CFE) upon treatment with oxaliplatin (L-OHP), while its relative reverse efficiency(RRE) was significantly higher (P<0.05) than the control cells, indicating compromised ability of cell proliferation. Indeed, Rho-damine 123 staining and flow cytometry analyses revealed an increased rate of apoptosis in hMMS2-depleted cells while no difference in cell proliferation or apoptosis was observed between the two control cell lines. The above observations collec-tively indicate that suppression of hMMS2 reverses L-OHP tolerance in differentiated human colorectal carcinoma cells by promoting apoptosis.

Diffusion imaging markers of accelerated aging of the lower cingulum in subjective cognitive decline.

Introduction: Alzheimer's Disease (AD) typically starts in the medial temporal lobe, then develops into a neurodegenerative cascade which spreads to other brain regions. People with subjective cognitive decline (SCD) are more likely to develop dementia, especially in the presence of amyloid pathology. Thus, we were interested in the white matter microstructure of the medial temporal lobe in SCD, specifically the lower cingulum bundle that leads into the hippocampus. Diffusion tensor imaging (DTI) has been shown to differentiate SCD participants who will progress to mild cognitive impairment from those who will not. However, the biology underlying these DTI metrics is unclear, and results in the medial temporal lobe have been inconsistent. Methods: To better characterize the microstructure of this region, we applied DTI to cognitively normal participants in the Cam-CAN database over the age of 55 with cognitive testing and diffusion MRI available (N = 325, 127 SCD). Diffusion MRI was processed to generate regional and voxel-wise diffusion tensor values in bilateral lower cingulum white matter, while T1-weighted MRI was processed to generate regional volume and cortical thickness in the medial temporal lobe white matter, entorhinal cortex, temporal pole, and hippocampus. Results: SCD participants had thinner cortex in bilateral entorhinal cortex and right temporal pole. No between-group differences were noted for any of the microstructural metrics of the lower cingulum. However, correlations with delayed story recall were significant for all diffusion microstructure metrics in the right lower cingulum in SCD, but not in controls, with a significant interaction effect. Additionally, the SCD group showed an accelerated aging effect in bilateral lower cingulum with MD, AxD, and RD. Discussion: The diffusion profiles observed in both interaction effects are suggestive of a mixed neuroinflammatory and neurodegenerative pathology. Left entorhinal cortical thinning correlated with decreased FA and increased RD, suggestive of demyelination. However, right entorhinal cortical thinning also correlated with increased AxD, suggestive of a mixed pathology. This may reflect combined pathologies implicated in early AD. DTI was more sensitive than cortical thickness to the associations between SCD, memory, and age. The combined effects of mixed pathology may increase the sensitivity of DTI metrics to variations with age and cognition.